Type 1 diabetes arises in genetically predisposed individuals as a consequence of T-cell mediated immune-mediated destruction of the pancreatic islet insulin secreting beta-cells. The onset of clinical symptoms of diabetes represents the endpoint of a chronic progressive decline in beta-cell function, and occurs when the majority of beta-cells have been lost. The Diabetes Prevention Trial -Type 1 (DPT-1) has shown that Type 1 diabetes can be predicted with a high degree of accuracy in relatives of patients with Type 1 diabetes by the presence of autoantibodies and evidence of pancreatic beta-cell dysfunction. The study has shown that cooperative research in Type 1 diabetes can be efficiently coordinated on a national and international level and has enabled identification of a large number of type-1 diabetes patients at the very early stages of their disease. Evidence, both in animal models of type-1 diabetes and in human trials, has shown that it is possible to alter the course of beta-cell destruction utilizing various interventions. DPT-1 has sought to determine whether insulin, when used as an antigen-based therapy, can delay the development of type 1 diabetes in at-risk individuals. Many potential interventions have not been considered because of their toxicities. Recently, several novel immunologic agents, that appear to be promising in the treatment of autoimmune diabetes, have been characterized in investigations of other autoimmune disorders and in the field of organ transplantation. The next logical step is to build upon the success of DPT-1 in identifying at-risk individuals by expanding its infrastructure to investigate additional agents that may lead to the prevention of the disease. Type-1 Diabetes TrialNet will assume this role and will further define the epidemiology and immunologic basis of Type 1 diabetes. We propose to participate in Type 1 Diabetes TrialNet as a Clinical Center. We have successfully served as a RRCC site in DPT-1 and we wish to apply our strengths in subject recruitment and clinical investigation to the collaborative effort represented by TrialNet. An important part of our application is the plan to investigate the potential role of Daclizumab (Zenapax) in the prevention of type 1 diabetes. We have enrolled and randomized 10 individuals to this novel treatment trial over the last 7 months. Our commitment to this line of investigation is evidenced by our efforts and success in designing and successfully implementing this protocol. Our participation as a Clinical Center in TrialNet will enable us to contribute our resources in a united attempt to improve our knowledge of type 1 diabetes and prevent the disease.